Malaria transmission is falling in some parts of Africa as bed nets and anti-malarials become more widely available. However, transmission still persists and it appears that additional control measures are required. The leading malaria vaccine candidate in development is RTS,S which has efficacy against clinical malaria measured at 30-50% in the field. This partial protection might be enhanced by combination with other components. The other vaccination approach that has produced repeatable efficacy in humans is the use of viral vectors to induce T cell responses. Previous attempts with this vaccine approach have been effective in challenge studies in Oxford, but ineffective in the field, probably because of reduced immunogenicity with previous vector platforms.

Recently, studies in Oxford, Kenya and the Gambia have shown higher levels of immunogenicity by using a chimpanzee adenovirus (ChAd63) followed by an attenuated vaccinia virus (modified vaccinia Ankara) to deliver the pre-erythrocytic antigen, multiple epitope string with thrombospondin- related adhesion protein (ME-TRAP).

The increase in immunogenicity has lead to sterile protection in 3 out of 14 volunteers and partial protection in 5 out of 14 volunteers in challenge studies.

The investigators propose a Phase 2b study of 120 healthy adult men in Senegal. The investigators will assess the efficacy and further evaluate the immunogenicity and safety profile of the vaccine regimen. The investigators also intend to assess the correlates of efficacy and natural immunity.

We will compare combined active vaccination from VAC046 and VAC047, with combined control vaccination from VAC046 and VAC047, for time to first episode of P.falciparum infection, defined as 2 or more consecutive blood samples confirmed positive by PCR for P.falciparum.

Able and willing (in the Investigator's opinion) to comply with all study requirements

Informed Consent

Exclusion Criteria:

Any significant medical disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data

Hypersensitivity to HDCRV,the trial vaccines or the antimalarial used.

History of allergic disease or reactions likely to be exacerbated by any component of the vaccines, e.g. egg products, kathon, neomycin

History of vaccination with previous experimental malaria vaccines or other vaccines likely to impact on findings of study (e.g. other MVA or adenovirus vectored vaccines)

Administration of any other vaccine or immunoglobulin within 2 weeks before vaccination.

HIV or Hepatitis B surface antigen seropositivity.

Current participation in another clinical trial or recent participation within 12 weeks of this study.

Any other finding which in the opinion of the investigators would increase the risk of an adverse outcome from participation in the trial.

Likelihood of travel away from the study area

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01658696